Dicyclohexylamine → 4-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

HRID 1965168노트

반응식

HRID 1965168 반응식
[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([OH:9])=O)[C:3]([CH3:6])([CH3:5])[CH3:4].C1CCC(NC2CCCCC2)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:64]([O:68][C:69]([N:71]1[CH2:75][CH:74]([O:76][C:77]2[CH:82]=[CH:81][C:80]([F:83])=[C:79]([F:84])[CH:78]=2)[CH:73]2[NH:85][CH2:86][CH2:87][CH:72]12)=[O:70])([CH3:67])([CH3:66])[CH3:65]>CN1C(=O)CCC1.CCOC(C)=O.CCOCC>[C:64]([O:68][C:69]([N:71]1[CH2:75][CH:74]([O:76][C:77]2[CH:82]=[CH:81][C:80]([F:83])=[C:79]([F:84])[CH:78]=2)[CH:73]2[N:85]([C:7](=[O:9])[CH:2]([NH:1][C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[C:3]([CH3:4])([CH3:5])[CH3:6])[CH2:86][CH2:87][CH:72]12)=[O:70])([CH3:67])([CH3:65])[CH3:66]

참가 물질

9

반응물 5

HCID 7582DicyclohexylamineHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 9899995(2S)-2-(((benzyloxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 676064563-(3,4-Difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

생성물 1

HCID 676074394-(2-Benzyloxycarbonylamino-3,3-dimethyl-butyryl)-3-(3,4-difluoro-phenoxy)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매2회

실험 절차

To a solution containing Cbz-Tle-OH.DCHA salt (4.1 g, 9.0 mmol) and HATU (3.8 g, 10 mmol) in NMP (50 mL) was added NMM (1.5 mL), followed by a solution of crude 22 (2.6 g, 7.5 mmol) in NMP (50 mL) at room temperature. The reaction mixture was stirred at room temperature. After 16 h, the reaction mixture was diluted with 10% EtOAc in Et2O, washed successively with water, 1N HCl, 1N NaOH, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue was purified by RP-HPLC (2″ Dynamax® C18; 10-100% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min) to afford 3.5 g of 23 as white foam. Mass spectrum, m/z [688.3] (M+H)+.

후처리

  1. washwashed successively with water, 1N HCl, 1N NaOH, and brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by RP-HPLC (2″ Dynamax® C18
  6. wait10-100% ACN/water containing 0.1% HOAc over 30 min

출처 및 근거

ORD 기록
ord-33c5dd7a1f61474b9e8d7757c3a9f7a5
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415486B2

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